Dear Yiannis,

In the process of replicative senescence ,there is a tight correlation with the inactivation of p53 and the expression levels of p16INK4a. Post.Post replicative senescence,inactivation of p53 and the low level of p16 will re-promote the proliferation and the high level leads to the inverse.The research on different cues promoting lower/higher p16INK4a will better enable us to understand resumption of senescence.There could also be a relation response with telomerase.

Regards

Charan

Thank you very much Charan. Your answer is very helpful.

Best regards

Yiannis

Theoretically yes. What is causing senescence in the first place? It is the attrition of the telomeric sequence at a rate of 100 to 120 NT per replication cycle. Once the telomeres reach a critical length cells go into cell cycle arrest or apoptosis. Having said that an elongation of telomeres would reverse this process. Cancer cells for example do this trick by activating the telomerase. Another way is the ALT pathway. So YES, in principle senescence can be reversed.

Thank you for the informative answer Ludger.

Replicative senescent human normal diploid fibroblasts in vitro are stably arrested. This is the only case I know for sure (maybe someone else is aware of other examples of long term sustaining senescent cells in vitro). Many other normal and tumor cells with senescent morphology can spontaneously return back into replication as can be observed, for example, by time-lapse microscopy. Alternatively, Brdu/Edu incorporation in such senescent cell populations rarely goes to zero (there is frequently an equilibrium of cell death and proliferation). The situation in vivo is completely obscure. I suppose senescence can be reversed, for example, by extrinsic inhibition of expression of cdk inhibitors...

Is ageing a non-programmed phenomenon (the effect of the accumulation of various damages) or a programmed phenomenon (i.e., genetically determined and regulated, and favoured in terms of supra-individual selection)?

The current opinion is the first option, but I think that evidence and theoretical arguments are strongly against the first and in support of the second option.

In the first case, senescence is hardly tameable, while the opposite is true in the second case.

You may find papers about this topic in my personal page (www.r-site.org/ageing) and in a specific page of the site www.programmed-aging.org, i.e. www.programmed-aging.org/theory-2/aging_theory_chronology.html.

In particular, please,see:

 1998 - Telomerase introduction in somatic cells makes them able to innumerable duplications and reverts manifestations of cell senescence (Bodnar et al. 1998, Counter et al. 1998 , Vaziri & Benchimol 1998, de Lange & Jacks 1999) 

2011 - Telomerase reactivation in aged mice with artificially blocked telomerase shows a marked reversal of degenerative manifestations, even for nervous system (Jaskelioff et al. 2011)

and read:

G. Libertini (2009) The Role of Telomere-Telomerase System in Age-Related Fitness Decline, a Tameable Process, in Telomeres: Function, Shortening and Lengthening, Nova Science Publ., New York

G. Libertini (2009) Prospects of a Longer Life Span beyond the Beneficial Effects of a Healthy Lifestyle, in Handbook on Longevity: Genetics, Diet & Disease, Nova Science Publ., New York.

Let me know your considerations

Thank you very much Dr Libertini.

I will look into this information.

Cellular senescence is more than simple proliferative arrest and while some cancers may arise through escaping the senescence mediated cell-cycle arrest, this is not a reversion.  Senescence is also associated with an immunogenic phenotype and commonly a pro-survival response likely as a result of DNA damage.  We can only say senescence is "reversible" when it becomes phenotypically and functionally identical to its pre-senescent state that no longer contains DNA damage.  To date this has not been shown.  Therefore, senescence is a permanent state...at least until they are likely eliminated by the immune system. 

Oncogene-induced senescence (OIS) can be attenuated by the depletion of oncogenic signal.